Tremendous strides in the understanding of DNA structures responsible for expression of antibody molecules have been made through use of DNA cloning and sequencing techniques. In this research, we extended the recombinant DNA approach to the study of human immunoglobulin genes in normal and leukemic cells. We are characterizing the heavy chain genes for human IgM and IgD by isolating and sequencing genomic and cDNA clones of this region and have found that the human delta gene has three constant region domains and an extended hinge, while the mouse delta gene has only two constant region domains and a hinge. We studied the immunoglobulin heavy chain variable region (VH) genes in patients with familial chronic lymphocytic leukemia (CLL). We cloned the expressed partially sequenced VH genes from two brothers with familial CLL and showed that they express extremely similar or identical VH genes. This supports the concept that some aspect of the antigen receptor, such as a particular idiotype or affinity for a particular antigen or T-cell factor, is involved in development of this cancer. (AB)